Melatonin attenuates morphine-induced conditioned place preference in Wistar rats

Morphine is the predominantly used drug for postoperative and cancer pain management. However, the abuse potential of morphine is the primary disadvantage of using opioids in pain management. Melatonin is a neurohormone synthesized in the pineal gland and is involved in circadian rhythms in mammals, as well as other physiological functions. Melatonin provenly attenuates alcohol-seeking and relapse behaviors in rats. Therefore, we aimed to investigate the involvement of the melatonergic system in attenuating morphine dependence.

Male Wistar rats were divided into three groups: control, morphine, and morphine + melatonin. Animals were habituated for 3 days, and the initial preference was evaluated. Following the initial preference, the control group received the vehicle and was placed for a 45-min session in the assigned chamber every day, alternating between the two chambers, for 8 days. The morphine group received a morphine injection (5 mg/kg, IP) and was placed for a 45-min session in the white chamber, for a total of four sessions. The morphine + melatonin group received the morphine injection (5 mg/kg, IP) for a total of four sessions over an 8-day period. In the posttest session, the control and morphine groups received a vehicle injection 30 min before placement in the conditioned place preference (CPP). The morphine + melatonin group received a single injection of melatonin (50 mg/kg, IP) 30 min before the preference test.

Statistical analysis revealed that repeated administration of morphine for four sessions produced a significant increase in the CPP score in the morphine group compared to the control group. However, a single melatonin injection administered 30 min before the posttest attenuated morphine-seeking behavior and reduced morphine-induced place preference.

These findings provide novel evidence for the role of the melatonergic system as a potential target in modulating morphine-seeking behavior.